Abstract PS2-06-03: Sacituzumab Govitecan Dosing and Neutropenia Risk in Patients with HER2-Negative Metastatic Breast Cancer

Abstract Background: Sacituzumab govitecan (SG), a TROP2-directed antibody drug conjugate with topoisomerase I inhibitor payload, has demonstrated improved efficacy over standard chemotherapy in HR-positive and triple-negative breast cancer based on the TROPiCS-02 and ASCENT trials, respectively. However, neutropenia represents a significant dose-limiting toxicity that may necessitate dose modifications or hospitalization. Given increasing real-world use and associated adverse effects, varying dosing and supportive care strategies have emerged. Methods: This single-center retrospective cohort study analyzed HER2-negative metastatic breast cancer patients receiving SG (April 2020-December 2024) evaluating patient demographics, disease characteristics, treatment patterns, safety outcomes, and G-CSF use. Inverse probability weighting (IPW) based on propensity scores was applied to control for confounding variables. Results: Among 366 patients, most initiated SG at 10 mg/kg (70%), with fewer starting at 7.5 mg/kg (22%) or 5 mg/kg (8%) (Table 1). Dose reductions were more common when starting at 10 mg/kg (42%) compared with 7.5 mg/kg (16%) and were primarily due to neutropenia (66%) followed by diarrhea (22%) and fatigue (17%). Three patients discontinued treatment due to toxicity. After adjustment for age, prior treatment lines and prophylactic G-CSF use, patients starting at 10 mg/kg had 2.8-fold higher odds of grade 3-4 neutropenia compared with 5 mg/kg (OR 2.77, 95% CI 1.29-6.27, p=0.011), while the duration of treatment was shorter at 5 mg/kg. Age was not associated with neutropenia risk or hospitalization rate after adjusting for starting dose, prophylactic G-CSF use, and prior treatment lines. Neither starting dose nor prior treatment lines significantly affected hospitalization rates. Prophylactic G-CSF was significantly associated with less grade 3-4 neutropenia (OR 0.12, 95% CI 0.07-0.18, p<0.001) when controlling for age, prior treatment lines, and starting dose and numerically fewer hospitalizations. Prophylactic G-CSF was most frequently used in patients who started treatment at reduced doses, but utilization rates did not differ by age. Conclusions: This real-world analysis demonstrates a clear dose-dependent relationship with severe neutropenia, with 10 mg/kg dosing conferring a significantly higher risk compared to 5 mg/kg. Age was not associated with increased risk of neutropenia or hospitalization. These findings do not support empiric dose reduction based solely on advanced age. Primary prophylactic G-CSF provides substantial protection against severe neutropenia regardless of starting dose or age. Citation Format: A. B. Newman, A. Raghavendra, E. Grannan, F. Meric-Bernstam, D. Tripathy, J. Litton, S. Damodaran. Sacituzumab Govitecan Dosing and Neutropenia Risk in Patients with HER2-Negative Metastatic Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-06-03.